System and method for pacing parameter optimization using heart sounds

ABSTRACT

A medical device system and associated method predict a patient response to a cardiac therapy. The system includes for delivering cardiac pacing pulses to a patient&#39;s heart coupled to a cardiac sensing module and a cardiac pacing module for generating cardiac pacing pulses and controlling delivery of the pacing pulses at multiple pace parameter settings. An acoustical sensor obtains heart sound signals. A processor is enabled to receive the heart sound signals, derive a plurality of heart sound signal parameters from the heart sound signals, and determine a trend of each of the plurality of heart sound signal parameters with respect to the plurality of pace parameter settings. An external display is configured to present the trend of at least one heart sound parameter with respect to the plurality of pace parameter settings.

CROSS-REFERENCE TO PRIORITY APPLICATION

This application claims priority to U.S. provisional application No.61/512,971, filed Jul. 29, 2011; which is incorporated by referenceherein.

FIELD OF THE DISCLOSURE

The disclosure relates to a medical device system and associated methodfor optimizing cardiac therapy pacing parameters based on heart sounds.

BACKGROUND

Cardiac resynchronization therapy (CRT) is one therapy used to treatheart failure (HF) patients. During CRT, pacing pulses are delivered toone or more heart chambers to restore synchrony of the heart chambers.Guidelines for selecting patients for CRT have been established, e.g.New York Heart Association (NYHA) classification III to IV, leftventricular ejection fraction (LVEF) 35% or less, and a wide QRS complexof 120 ms or more. Despite these guidelines, not all patients benefitfrom CRT. Some patients, “responders,” present clinically significanthemodynamic improvement to CRT therapy while others are considered“non-responders” presenting little or no improvement. Because of thevaried response to CRT between patients meeting current guidelines,patient selection for CRT continues to be challenging to clinicians.

Once a patient is selected for a pacing therapy, optimizing timing ofpacing parameters is important in achieving therapeutic benefit of apacing therapy, or at least preventing unintentional deleterioushemodynamic effects of a pacing therapy. Pacing timing controlparameters include the atrial-ventricular (AV) interval used duringsingle chamber ventricular pacing, during dual chamber (atrial andventricular) pacing, and multi-chamber pacing, and the intra-ventricular(VV) interval used during biventricular or multi-chamber pacing. The AVinterval is a pacing control time interval started upon sensing anatrial event (P-wave) or delivering an atrial pacing pulse (A-pace).Upon expiration of the AV interval, the pacing device delivers aventricular pacing pulse (V-pace) if an intrinsic ventricular event(R-wave) is not sensed during the AV interval. Similarly, the VVinterval is used to control the timing of a ventricular pacing pulsefollowing a programmed VV interval after a paced or sensed R-waveoccurring in the opposite ventricular chamber.

Echocardiography continues to be a “gold standard” for optimizing pacingtiming parameters. Echocardiography, however, tends to be a costly andtime-consuming procedure which requires specially trained sonographersto perform. Other methods for monitoring hemodynamic performance of theheart typically require invasive techniques such as cardiaccatheterization for measuring left ventricular (LV) pressure, cardiacoutput or other standard hemodynamic measurements. As such, thefrequency that such techniques can be used to determine the best pacingparameters for an individual patient are limited due to time, cost,burden on the patient, and/or inherent risks associated with invasivemethods. It would be desirable for a clinician to know with a relativelyhigh certainty beforehand whether a patient will be responsive to agiven therapy and how best to manage the therapy to avoid costly,time-consuming and invasive procedures.

Other methods proposed for selecting CRT patients and optimizing CRTtherapy include measuring the QRS width and performing adjustments tocause a narrowing of the QRS width. This technique assumes that a widerQRS width indicates greater ventricular dyssynchrony and a narrowing ofthe QRS width will be associated with improved ventricular synchrony. Ina significant number of patients, however, electrical dyssynchrony andmechanical dyssynchrony do not strongly correlate. As such, patientselection and optimization based on QRS width may have limited utility.

A need remains, therefore, for a medical device system and associatedmethod for optimizing pacing parameters using low-cost and non-invasivemethods which improve patient benefit to cardiac pacing therapies fortreating heart failure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a functional block diagram of an implantable medical device(IMD) system for acquiring heart sounds and delivering a cardiac pacingtherapy for treating heart failure according to one embodiment.

FIG. 2 is a schematic diagram of one embodiment of an implantablemedical device (IMD) system in which techniques disclosed herein may beimplemented to provide therapy to the heart of a patient.

FIG. 3 is a flow chart of a method for optimizing pace controlparameters according to one embodiment.

FIG. 4 is a display of HS signals recorded for varying AV intervalsettings.

FIG. 5 is a plot of HS parameter trends generated from the data shown inFIG. 4.

FIG. 6 is a display of HS signals recorded for varying VV intervalsettings during a VV interval optimization procedure.

FIG. 7 is a flow chart of a method for selecting pace control parametersusing HS signal analysis according to an alternative embodiment.

DETAILED DESCRIPTION

In the following description, references are made to illustrativeembodiments. It is understood that other embodiments may be utilizedwithout departing from the scope of the disclosure. As used herein, theterm “module” refers to an application specific integrated circuit(ASIC), an electronic circuit, a processor (shared, dedicated, or group)and memory that execute one or more software or firmware programs, acombinational logic circuit, or other suitable components that providethe described functionality.

FIG. 1 is a functional block diagram of an IMD system 10 for acquiringheart sounds and delivering a cardiac pacing therapy for treating heartfailure according to one embodiment. IMD 10 includes a heart sound (HS)sensing module 12 coupled to an acoustical sensor 11 responsive to heartsounds, cardiac signal sensing circuitry 14 and pulse generator 15 bothcoupled to electrodes 13, control processor 16 and associated memory 18,and telemetry circuitry 20. HS sensing module 12 receives signals froman acoustical sensor 11 for sensing heart sounds which are provided tocontrol processor 16 for optimizing CRT pace parameters based on heartsounds.

Physicians are particularly familiar with evaluating heart sounds aspart of a basic physical examination, and a stethoscope is a standardcomponent in a physician's diagnostic tool box. Using a heart soundsensor as a component of a medical device system for automaticallyoptimizing CRT pace parameters will enable clinicians to quickly obtainan overview of the patient's hemodynamic response to varying paceparameters and gain an indication of optimal parameter settings and howthe therapy should be managed for the particular patient as will befurther described herein.

Clinicians typically refer to four heart sounds, S1, S2, S3 and S4. Aswill be described herein, the amplitudes and/or relative time intervalsof one or more of the S1 through S4 heart sounds can be useful inoptimizing a patient's hemodynamic response to CRT or other cardiactherapies that include cardiac pacing and/or neural stimulation forachieving hemodynamic benefit. The first heart sound, S1, corresponds tothe start of ventricular systole. Ventricular systole begins when anaction potential conducts through the atrioventricular node (AV node)and quickly depolarizes the ventricular myocardium. This event isdistinguished by the QRS complex on the ECG. As the ventricles contract,pressure in the ventricles begins to rise, causing abrupt closure of themitral and tricuspid valves between the ventricles and atria asventricular pressure exceeds atrial pressure. This valve closuregenerates S1. S1 generally has a duration of about 150 ms and afrequency on the order of 20 to 250 Hz. The amplitude of S1 may providea surrogate measurement of LV contractility. Thus an increase in S1amplitude positively correlates with an improvement in LV contractility.

Separation of the closure of the mitral and tricuspid valves due toventricular dyssynchrony can be observed as separate M1 and T1 peaks inthe S1 signal. Merging of the M1 (mitral valve closure sound) and the T1(tricuspid valve closure sound) can be used as an indication of improvedventricular synchrony.

Left ventricular pressure (LVP) rises dramatically following the QRScomplex of the ECG and closure of the mitral valve and continues tobuild during ventricular systole until the aortic and pulmonary valvesopen, ejecting blood into the aorta and pulmonary artery. Ventricularcontraction continues to cause blood pressure to rise in the ventriclesand the aorta and pulmonary artery during the ejection phase. As thecontraction diminishes, blood pressure decreases until the aortic andpulmonary valves close. The second heart sound, S2, is generated by theclosure of the aortic and pulmonary valves, near the end of ventricularsystole and start of ventricular diastole. S2 is therefore correlated todiastolic pressure in the aorta and the pulmonary artery. S2 generallyhas a duration of about 120 ms and a frequency on the order of 25 to 350Hz. The time interval between S1 and S2, i.e. S1-S2 time intervalrepresents the systolic time interval (STI) corresponding to theventricular isovolumic contraction (pre-ejection) and ejection phase ofthe cardiac cycle. This S1-S2 time interval provides a surrogatemeasurement for stroke volume.

One method used by clinicians for optimizing the AV interval during CRTinvolves pulsed Doppler echocardiography and adjusting the AV intervalto increase the separation of the A-wave and the E-wave without A-wavetruncation. The E-(early) wave and the A-(atrial) wave represent themeasurement of blood flow velocity across the mitral valve, with theE-wave occurring during passive filling of the ventricle and the A-waveoccurring during active ventricular filling due to the atrialcontribution or “atrial kick” during atrial systole. Greater separationof the E-wave and A-wave is thought to improve ventricular filling, whentruncation of the A-wave due to onset of ventricular contraction isavoided. The occurrence of a sudden change in the timing of S2 relativeto a ventricular sensed event (R-wave) or ventricular pacing pulse isused as a surrogate of the measurement of maximum time separation of theE-wave and A-wave without A-wave truncation in one embodiment asdescribed in greater detail below.

The third heart sound, S3, is associated with early, passive diastolicfilling of the ventricles, and the fourth heart sound, S4, is associatedwith late, active filling of the ventricles due to atrial contraction.The third sound is generally difficult to hear in a normal patient usinga stethoscope, and the fourth sound is generally not heard in a normalpatient. Presence of the third and fourth heart sounds during anexamination using a stethoscope may indicate a pathological condition.The S3 and S4 heart sounds may be used in optimizing pace parameters asthey relate to diastolic function of the heart. Generally, these soundswould be minimized or disappear when an optimal pace parameter isidentified. Other aspects of the S1 through S4 heart sounds and timingthereof that may be useful in cardiac pace parameter optimization aredescribed in the above-incorporated '260 application.

HS sensing module 12 is configured to receive analog signals from sensor11 for sensing one or more of these heart sounds. For example, HSsensing module 12 may include one or more “channels” configured toparticularly sense a specific heart sound based on frequency, duration,and timing of the heart sounds. For example, ECG/EGM sensing circuitry14 may be used by control processor 16 to set HS sensing windows used byHS sensing module 12 for sensing the heart sounds. HS sensing module 12may include one or more sense amplifiers, filters and rectifiers foroptimizing a signal to noise ratio of heart sound signals. Separate andunique amplification and filtering properties may be provided forsensing each of the S1 through S4 sounds to improve signal quality asneeded.

In various embodiments, acoustical sensor 11 may be implemented as amicrophone or a 1-, 2- or 3-axis accelerometer. In one embodiment,acoustical sensor 11 is implemented as a piezoelectric crystal mountedwithin an implantable medical device housing and responsive to themechanical motion associated with heart sounds. The piezoelectriccrystal may be a dedicated HS sensor or may be used for multiplefunctions. In the illustrative embodiment shown, acoustical sensor 11 isembodied as a piezoelectric crystal that is also used to generate apatient alert signal in the form of a perceptible vibration of the IMDhousing. Upon detecting an alert condition, control processor 16 causespatient alert control circuitry 24 to generate an alert signal byactivating the piezoelectric crystal.

Switching circuitry 26 is used to control whether the piezoelectriccrystal is used in a “listening mode” to sense HS signals by HS sensingcircuitry 12 or in an “output mode” to generate a patient alert. Duringpatient alert generation, HS sensing circuitry 12 is temporarilydecoupled from acoustical sensor 11 by switching circuitry 26.

Examples of other embodiments of acoustical sensors that may be adaptedfor implementation with the techniques of the present disclosure aregenerally described in U.S. Pat. No. 4,546,777 (Groch, et al.), U.S.Pat. No. 6,869,404 (Schulhauser, et al.), U.S. Pat. No. 5,554,177(Kieval, et al.), and U.S. Pat. No. 7,035,684 (Lee, et al.), all ofwhich patents are hereby incorporated by reference in their entirety.Practice of the methods and techniques described herein are not limitedto a particular type of acoustical sensor. Acoustical sensor 11 may beany implantable or external sensor responsive to one or more of theheart sounds generated as described in the foregoing and therebyproduces an electrical analog signal correlated in time and amplitude tothe heart sounds. The analog signal may be then be processed, which mayinclude digital conversion, by HS sensing module 12 to obtain HSparameters, such as amplitudes or relative time intervals, as derived byHS sensing module 12 or control processor 16. The acoustical sensor 11and HS sensing module 11 may be incorporated in an IMD capable ofdelivering CRT or another cardiac therapy being optimized or may beimplemented in a separate device having wired or wireless communicationwith IMD 10 or an external programmer or computer (not shown in FIG. 1)used during a pace parameter optimization procedure as described below.

ECG/EGM sensing circuitry 14, coupled to at least one sensing electrodepair included in electrodes 13, is provided to sense cardiac signals,e.g. P-wave and/or R-wave signals attendant to the depolarization of theatria and ventricles of the heart, respectfully. Sensing circuitry 14 iscoupled to electrodes 13, which may include transvenous intracardiacelectrodes, epicardial electrodes, or subcutaneous/submuscularelectrodes, for sensing cardiac EGM or ECG signals. ECG signals and EGMsignals are referred to herein generally as “cardiac electricalsignals”. Cardiac electrical signals are sensed for use in timing pacingpulses delivered during HS signal recording for optimizing paceparameters. Cardiac electrical signals may additionally be used fortiming sensing windows used by HS sensing module 12 for obtaining HSsignals. Cardiac electrical signals may additionally or alternatively beused by control processor 16 for determining time intervals relative tosensed heart sounds and these time intervals may be used as surrogatehemodynamic parameters in pace parameter optimization. Sensed cardiacsignals are also used in timing pacing pulses during therapy deliveryaccording to programmed pacing intervals, such as programmed AV intervaland VV interval.

Pulse generator 15 is provided for delivering pacing pulses to thepatient's heart via electrodes 13 using programmable pacing parameters.HS signals are recorded during variation of selected pacing parametersto determine a hemodynamic response to changes in at least one paceparameters. The HS signal response to variation of a pace parameter isused to determine an optimal pace parameter setting for achievinghemodynamic benefit from the cardiac pacing therapy. Accordingly, pulsegenerator 15 is coupled to cardiac pace electrodes included inelectrodes 13, which may include transvenous intracardiac electrodes,epicardial electrodes, and/or subcutaneous/submuscular electrodes orother transvenous or extravascular electrodes in the case of aneurostimulation delivered as a cardiac therapy. The electrodes 13 usedfor delivering pacing pulses may be dedicated pacing electrodes, or mayinclude shared pacing and sensing electrodes. Switching circuitry (notshown) may be used for selecting which electrodes 13 are coupled toECG/EGM sensing circuitry 14 and which electrodes are coupled to pulsegenerator 15 as well as the polarity of such electrodes. While twoelectrodes are shown coupled to pulse generator 15 and two electrodesare shown coupled to ECG/EGM sensing module 14 in FIG. 1, it isrecognized that multiple sensing and pacing channels corresponding tomultiple heart chambers will require multiple electrodes coupled to eachof sensing module 14 and pulse generator 15 and such connections may becontrolled by a switching circuit, particularly when multipolarelectrodes are positioned relative to a single heart chamber.

Pulse generator 15 is controlled by control processor 16 to deliverpacing pulses according to a test algorithm during which heart soundsare recorded for generating trends of a HS parameter with respect to thepace parameter. Control processor 16 receives signals from ECG/EGMsensing circuitry 14 for use in controlling pulse generator 15 todeliver appropriately timed pacing pulses. Appropriately timed pacingpulses are pulses that are typically delivered at a rate greater than anintrinsic depolarization rate such that the pacing pulses control thetiming of heart chamber activation. As such, a lower pacing rate and/ora pacing timing interval such as an AV interval or VV interval may becontrolled such that a pacing pulse precedes an intrinsic activation ofthe heart the majority of the time to maintain a desired heart rate andinter-chamber timing intervals. Appropriately timed pacing pulses arealso delivered outside the vulnerable period of the heart to avoid riskof arrhythmia induction.

Control processor 16 may include any one or more of a microprocessor, adigital state machine, a digital signal processor (DSP), an applicationspecific integrated circuit (ASIC), a field-programmable gate array(FPGA), or equivalent discrete or integrated logic circuitry. In someexamples, processor 16 may include multiple components, such as anycombination of one or more microprocessors, one or more controllers, oneor more DSPs, one or more ASICs, or one or more FPGAs, as well as otherdiscrete or integrated logic circuitry. The functions attributed tocontrol processor 16 herein may be embodied as software, firmware,hardware or any combination thereof, implemented in a single device ordistributed across two or more devices, which may include one or moreimplantable devices, external devices, or a combination of both.

Control processor 16 includes a HS analysis module 22 for analyzingheart sound signals obtains by HS sensing 12 to determine HS parameters.The HS parameters are used to determine an optimal setting for at leastone pacing control parameter. HS analysis module 22 includes circuitryand/or computer-readable instructions for performing an algorithm forderiving HS parameters and trends or relative changes in HS parameterswith a changing pace control parameter.

Memory 18 stores algorithms used by control processor 16 for performingpacing parameter optimization. Such algorithms may include pacingprotocols used to obtain HS signals responsive to different pacingconditions. Memory 18 may also be used to store other data andinformation used by control processor 16 for controlling devicefunctions, including a pacing or neurostimulation therapy delivered bypulse generator 15, controlling sensing functions by ECG/EGM sensingcircuitry 14, controlling telemetry module 20, and controlling patientalert 24 in response to detecting an alert condition based on HS signalsand/or cardiac electrical signals.

It is contemplated that IMD 10 may include or be coupled to othersensors 28 which provide signals to control processor 16 correlated toother physiological conditions of the patient. Sensors 28 may include anactivity sensor, posture sensor, pressure sensor, oxygen sensor,temperature sensor, impedance sensor or the like. Sensor signals may beused by control processor 16 to detect a physiological condition of thepatient indicating a need to provide or adjust therapy or generate apatient alert. In some embodiments, sensors 28 are used to determinecontrol conditions, such as activity level and/or posture, during whicha pace control parameter optimization procedure will be performed.

Telemetry module 20 is configured for bidirectional communication withan external programmer or computer operating software for programmingthe IMD 10. Control processor 16 may generate HS data and informationrelating to optimal pacing parameters that is transmitted to an externaldevice via telemetry module 20 for review by a clinician. In someembodiments, functions attributed herein to control processor 16 may beperformed across one or more processors that may include an externalprocessor receiving data from telemetry module 20.

FIG. 2 is a schematic diagram of one embodiment of an IMD system 100 inwhich techniques disclosed herein may be implemented to provide therapyto heart 112 of patient 114. System 100 includes IMD 10, shown by thefunctional block diagram of FIG. 1. IMD 10 is coupled to leads 118, 120,and 122 which carry multiple electrodes generally corresponding toelectrodes 13 of FIG. 1. IMD 10 is configured for bidirectionalcommunication with programmer 170. IMD 10 may be, for example, animplantable pacemaker, cardioverter, and/or defibrillator that provideselectrical signals to heart 112 via electrodes coupled to one or more ofleads 118, 120, and 122. IMD 10 is capable of delivering at least singlechamber ventricular pacing, and in the embodiment shown, is configuredfor multi-chamber pacing and sensing in the right atrium (RA) 126, theright ventricle (RV) 128, and the left ventricle (LV) 132 using leads118, 120 and 122.

IMD 10 delivers RV pacing pulses and senses RV intracardiac EGM signalsusing RV tip electrode 140 and ring electrode 142 positioned in the RV128. RV lead 118 is shown to carry a coil electrode 162 which may beused for delivering high voltage cardioversion or defibrillation shockpulses. IMD 116 senses LV EGM signals and deliver LV pacing pulses usingthe electrodes 144 carried by multipolar coronary sinus lead 120,extending through the RA 126 and into a cardiac vein 130 via thecoronary sinus. In some embodiments, coronary sinus lead 120 may includeelectrodes positioned along the left atrium (LA) 136 for sensing leftatrial (LA) EGM signals and deliver LA pacing pulses.

IMD 10 senses RA EGM signals and delivers RA pacing pulses using RA lead122, carrying tip electrode 148 and ring electrode 150. RA lead 122 isshown to be carrying coil electrode 166 which may be positioned alongthe superior vena cava (SVC) for use in deliveringcardioversion/defibrillation shocks. In other embodiments, RV lead 118carries both the RV coil electrode 162 and the SVC coil electrode 166.IMD 10 may detect arrhythmias of heart 112, such as fibrillation ofventricles 128 and 132, and deliver defibrillation therapy to heart 112in the form of electrical pulses. While IMD 10 is shown in a rightpectoral implant position in FIG. 2, a more typical implant position,particular when IMD 10 is embodied as an ICD, is a left pectoral implantposition.

IMD 10 includes internal circuitry for performing the functionsattributed to IMD 10 and a housing 160 encloses the internal circuitry.It is recognized that the housing 160 or portions thereof may beconfigured as an active electrode for use incardioversion/defibrillation shock delivery or used as an indifferentelectrode for unipolar pacing or sensing configurations. IMD 10 includesa connector block 134 having connector bores for receiving proximal leadconnectors of leads 118, 120 and 122. Electrical connection ofelectrodes carried by leads 118, 120 and 122 and IMD internal circuitryis achieved via various connectors and electrical feedthroughs includedin connector block 134.

In the embodiment shown, IMD 10 is also configured for delivering CRTtherapy, which may use a selected pacing vector for LV pacing thatincludes at least one electrode 144 on multipolar LV lead 120. IMD 10may be configured to pace in one or both ventricles 128 and 132 forcontrolling and improving ventricular synchrony. The methods describedherein may be implemented in a single, dual or multi-chamber pacemakeror ICD delivering pacing pulses using programmable pacing pulse timingparameters and/or programmable pacing vectors, collectively referred toherein as “pace control parameters”. Pace control parameter are notlimited to timing-related parameter and pacing vector selections and mayadditionally include any control parameter used by the control processor16 in controlling the delivery of pulses by pulse generator 15 (FIG. 1).

System 100 includes a HS sensor 158, which is shown to be incorporatedwithin housing 160 of IMD 10. As described above, HS sensor 158 may be amicrophone, accelerometer, e.g. a piezoelectric transducer sensitive tothe vibrations caused by motion of the heart structures, or otheracoustical sensor. In other embodiments, a HS sensor may be carried byan intra- or extravascular lead and is positioned in operative relationto heart 112 for obtaining signals representative of heart sounds.

IMD 10 may provide HS signal data to programmer 170 via wirelesstelemetry. HS data and/or a recommendation of one or more pace controlparameter settings may be transmitted to programmer 170 for display to auser. Thus, the pace control optimization procedures described hereinmay be automated in the IMD system 100 and not require a specializedtechnician to perform the analysis, as required for example duringechocardiography studies. The procedure may be performed automaticallyby IMD 10 with optimal pace control parameters identified andautomatically programmed by IMD 10. The optimization procedure mayalternatively be performed by IMD 10 with HS signal data and/orrecommended pace control parameter setting(s) transmitted to programmer170 for display to a user.

Programmer 170 includes a display 172, a processor 174, a user interface176, and a communication module 178 including wireless telemetrycircuitry for communication with IMD 10. In some examples, programmer170 may be a handheld device or a microprocessor based home monitor orbedside programming device. A user, such as a physician, technician,nurse or other clinician, may interact with programmer 170 tocommunicate with IMD 10. For example, the user may interact withprogrammer 170 via user interface 176 to retrieve physiological ordiagnostic information from IMD 10. A user may also interact withprogrammer 170 to program IMD 10, e.g., select values for operationalparameters of the IMD. A user interacting with programmer 170 mayrequest IMD 10 to perform a HS-based optimization algorithm and transmitresults to programmer 170 or request data stored by IMD 10 relating toHS analysis procedures performed automatically by IMD 10 on a periodicbasis. Processor 174 receives data from IMD 10 for use in generating adisplay presented on display 172 including information relating to HSdata.

Programmer 170 includes a communication module 178 to enable wirelesscommunication with IMD 10. Examples of communication techniques used bysystem 100 include low frequency or radiofrequency (RF) telemetry, whichmay be an RF link established via Bluetooth, WiFi, MICS, or as describedin U.S. Pat. No. 5,683,432 “Adaptive Performance-OptimizingCommunication System for Communicating with an Implantable MedicalDevice” (Goedeke, et al). In some examples, programmer 170 may include aprogramming head that is placed proximate to the patient's body near theIMD 10 implant site, and in other examples programmer 170 and IMD 10 maybe configured to communicate using a distance telemetry algorithm andcircuitry that does not require the use of a programming head and doesnot require user intervention to maintain a communication link.

It is contemplated that programmer 170 may be coupled to acommunications network via communications module 178 for transferringdata to a remote database or computer to allow remote management of apatient using the HS-based pacing parameter optimization techniquesdescribed herein. Remote patient management systems may be configured toutilize the presently disclosed techniques to enable a clinician toreview HS data and authorize programming of IMD pace control parameters.For example, HS signals or parameters derived there from may betransferred from programmer 170 to a clinic or other expert center forreview. Recommended pace control parameters may be authorized forprogramming in the IMD by a clinician or other expert then programmedusing remote IMD programming techniques via a communications network andprogrammer 170. Reference is made to commonly-assigned U.S. Pat. No.6,599,250 (Webb et al.), U.S. Pat. No. 6,442,433 (Linberg et al.) U.S.Pat. No. 6,622,045 (Snell et al.), U.S. Pat. No. 6,418,346 (Nelson etal.), and U.S. Pat. No. 6,480,745 (Nelson et al.) for generaldescriptions and examples of network communication systems for use withimplantable medical devices for remote patient monitoring and deviceprogramming, all of which patents are hereby incorporated herein byreference in their entirety.

FIG. 3 is a flow chart 200 of a method for optimizing pace controlparameters according to one embodiment. Flow chart 200 and other flowcharts presented herein are intended to illustrate the functionaloperation of the medical device, and should not be construed asreflective of a specific form of software or hardware necessary topractice the methods described. It is believed that the particular formof software will be determined primarily by the particular systemarchitecture employed and by the particular sensing and pacing deliverymethodologies employed by the device. Providing software, firmwareand/or hardware in any combination to accomplish the describedfunctionality in the context of any modern medical device system, giventhe disclosure herein, is within the abilities of one of skill in theart.

Methods described in conjunction with flow charts presented herein maybe implemented in a computer-readable medium that includes instructionsfor causing a programmable processor included in the medical devicesystem to carry out the methods described. A “computer-readable medium”includes but is not limited to any volatile or non-volatile media, suchas a RAM, ROM, CD-ROM, NVRAM, EEPROM, flash memory, and the like. Theinstructions may be implemented as one or more software modules, whichmay be executed by themselves or in combination with other software.

A pace parameter optimization method is initiated at block 202. Theoptimization process may be initiated in response to a user commandreceived via an external programmer. At a time of initial IMDimplantation or during office follow-up visits, or during a remotepatient monitoring session, a user may initiate a HS-base optimizationprocedure using an external programmer or networked computer.Additionally or alternatively, the process shown by flow chart 200 maybe an automated process started periodically or in response to sensing aneed for therapy delivery or therapy adjustment based on a sensedphysiological signal, which may include sensed HS signals.

At block 204 a pace control parameter to be optimized is selected. Acontrol parameter may be a timing-related parameter, such as AV intervalor VV interval. Pacing vector is another control parameter that may beselected at block 204 for optimization. For example, when a multi-polarlead is used, such as the CS lead 120 shown in FIG. 2, multiple bipolaror unipolar pacing vectors may be selected for pacing in a given heartchamber. The pacing site associated with a particular pacing vector mayhave a significant effect on the hemodynamic benefit of a pacingtherapy. As such, pacing vector is one pace control parameter that maybe optimized using methods described herein.

A pacing sequence is initiated at block 206 using an initial parametersetting for the test parameter selected at block 204. In one embodiment,the AV interval is being optimized, and ventricular pacing is deliveredat an initial AV interval setting. It is understood that an initial AVinterval setting may be selected at block 206 by first measuring anintrinsic AV interval in a patient having intact AV conduction, i.e. noAV block. An initial AV interval may be a default pacing interval, thelast programmed AV interval, or a minimum or maximum AV interval to betested. Alternatively, if the VV interval is selected for optimization,an intrinsic inter-ventricular conduction time may be measured first andpaced VV intervals may be iteratively adjusted beginning at a VVinterval longer, shorter or approximately equal to the intrinsic VVconduction time.

An iterative process for adjusting the selected test parameter to atleast two different settings is performed. The parameter may be adjustedto different settings in any desired order, e.g. increasing, decreasing,random etc. For example, during adjustment of AV interval, an initial AVinterval may be set to just longer than or approximately equal to ameasured intrinsic AV conduction time then iteratively decreased down toa minimum AV interval test setting. During pacing using each paceparameter setting, HS signals are acquired at block 208. The iterativeprocess advances to the next test parameter setting at block 212 untilall test parameter settings have been applied, as determined at block210, and HS signals have been recorded for each setting.

HS signals may be acquired for multiple cardiac cycles to enableensemble averaging or averaging of HS parameter measurements taken fromindividual cardiac cycles. It is understood that amplification,filtering, rectification, noise cancellation techniques or other signalprocessing steps may be used for improving the signal-to-noise ratio ofthe HS signals and these steps may be different for each of the heartsounds being acquired, which may include any or all of S1 through S4.

At least one HS parameter measurement is determined from the recorded HSsignals for each test parameter setting at block 214. The IMD processoror an external processor, e.g. included in programmer 170, or acombination of both may perform the HS signal analysis described herein.In one embodiment, S1 and S2 are recorded and HS parameters are measuredusing the S1 and S2 signals at block 214. For example, the amplitude ofS1, the V-S2 interval (where the V event may be a V pace or a sensedR-wave), and the S1-S2 interval are measured. The presence of S3 and/orS4 may additionally be noted or measurements of these signals may bemade for determining related parameters. HS signal parameters aredetermined for at least two different test parameter settings, e.g. atleast two different AV intervals, two or more different VV intervals, ortwo or more different pacing vectors.

At block 218, a trend for each HS parameter determined at block 210 as afunction of the pace parameter test settings is determined. In oneembodiment, a trend for each of the V-S2 interval, S1 amplitude andS1-S2 interval is determined. Other embodiments may include determininga separation of the M1 and T1 sounds during the S1 signal. Based on thetrends of the HS parameter(s) with respect to the varied pace controlparameter, an optimal pace parameter setting may be identifiedautomatically by the processor at block 220. Additionally oralternatively, the HS trends are reported and displayed at block 222 onan external device such as programmer 170 (in FIG. 2) or at a remotenetworked computer.

If the pace parameter being tested is, for example, pacing site orpacing vector when a multipolar electrode is positioned along a heartchamber, such as the quadripolar lead 120 along LV 132 shown in FIG. 2,a pacing site or vector may be selected based on maximizing a HS-basedsurrogate for ventricular contractility. In one embodiment, theamplitude of S1 is used as a surrogate for ventricular contractility,and a pacing site or vector associated with a maximum S1 is identifiedat block 220 as the optimal pacing vector setting.

Determining the trend of each HS parameter at block 218 may includedetermining whether the V-S2 interval trend presents a sudden slopechange, e.g. from a substantially flat trend to a decreasing trend. AnAV interval associated with a sudden change in the V-S2 interval trendmay be identified as an optimal AV interval setting. The optimal AVinterval may be further identified based on other HS trends, for examplea maximum S1 amplitude and/or a maximum S1-S2 interval.

In some embodiments, an automatically-identified optimal pace parametersetting may also be automatically programmed in the IMD at block 224. Inother embodiments, the clinician or user reviews the reported HS dataand recommended pace parameter setting(s) and may accept a recommendedsetting or select another setting based on the HS data.

FIGS. 4 and 5 show HS data that may be displayed, separately orcombined, to a clinician or other user on programmer display 126 (FIG.2) or on a remote networked computer. FIG. 4 is a display 300 of HSsignals recorded for varying AV interval settings. The data shown indisplay 300 may be generated by the IMD processor and transmitted to anexternal programmer or networked computer for viewing by a clinician.Alternatively the data may be generated from raw HS signal data by aprocessor included in an external programmer 170 or networked remotepatient management system.

S1 signals 302 and S2 signals 304 recorded during pacing at different AVinterval settings 306, ranging from 120 ms to 260 ms in this example,are displayed. The S1 and S2 signals 302 and 304 represent rectified andensemble averaged signals obtained during approximately 10 seconds ofpacing at the given AV interval setting. As can be observed on display300, the amplitude and morphology of both S1 302 and S2 304 change withvarying AV interval. Additionally, the S1-S2 time interval 312 changeswith AV interval. The S1-S2 time interval 312 is shown as being measuredbetween a detected maximum peak amplitude 308 and maximum peak amplitude310 of each of the respective S1 302 and S2 signals 304. In variousembodiments, different fiducial points may be defined for detection ofS1 and S2 signals for determination of an S1-S2 time interval 312.

Time “0” 316 corresponds to the time of the ventricular pacing pulse. AV-S2 time interval 314 measured from the ventricular pacing pulse to theS2 peak 310 is also observed to change with different AV intervalsettings 306. The V-S2 time interval 314 may be measured as a timeinterval between an RV pacing pulse or sensed RV R-wave and the S2 peakamplitude 310, or an LV pacing pulse or sensed LV R-wave and S2 peakamplitude or another fiducial S2 signal point.

The HS parameters S1 peak amplitude 308, S1-S2 interval 312 and V-S2interval 314 are determined for each AV interval setting 306. The trendof one or more of the HS parameters with AV interval is used foridentifying an optimal AV interval.

FIG. 5 is a HS parameter plot 400 generated from the data shown in FIG.4. The S1 amplitude trend 408, S1-S2 interval trend 412, and V-S2interval trend 414 are each shown plotted as a function of AV interval406 (also referred to herein as “AV delay”). As can be observed, the S1amplitude trend 408 is generally bell-shaped having a peak atapproximately 220 ms. S1-S2 interval trend 412 is generally increasing,reaching a peak at approximately 220 ms. The V-S2 interval trend 414 isflat with a sudden slope change to a decreasing trend at an inflectionpoint 420 occurring at approximately 220 ms.

In one embodiment, a V-S2 interval trend that exhibits a sudden change,e.g. from a substantially flat trend to a suddenly decreasing trend,represents a patient that will benefit from AV interval optimizationduring CRT. When the V-S2 interval trend 414 exhibits a sudden change,an optimal AV interval may be recommended as the AV interval at whichthe sudden change inflection point occurs. Furthermore, periodicoptimization of the AV interval may be recommended in this patient.

In other embodiments, additional analysis of other HS parameters isperformed to identify the optimal AV interval. For example, the AVinterval at which the sudden change inflection point 420 occurs may beidentified as an optimal AV interval. Longer AV intervals result indecreasing V-S2 interval which may be associated with a fusion period ofatrial intrinsic conduction and ventricular pace induced conduction. Theoptimal AV delay may correspond to the lower boundary of the fusionband. In the given example, the lower boundary of the fusion band (i.e.,the optimal AV interval) would be approximately 220 ms. One or moreother HS parameters are then examined to determine an optimal AVinterval at or less than 220 ms. For example, the S1-S2 interval trend412 is observed to reach a maximum peak value 422 at both 220 ms and 240ms. However 220 ms is the first AV interval at which the peak occurs. Assuch, 220 ms is identified as the optimal AV interval. The S1 amplitudetrend 408 may additionally or alternatively be examined to determine amaximum value that occurs at or below the optimal AV interval. In thisexample, the maximum S1 amplitude 424 correlates with a maximum S1-S2interval 422 and the inflection point 420 defining a maximum AV intervalbased on a sudden inflection point of the V-S2 interval trend 414.

FIG. 6 is a display 450 of HS signals recorded for varying VV intervalsettings 404 during a VV interval optimization procedure. As describedabove, data shown in display 450 may generated by the IMD processorand/or an external processor and displayed on a programmer or networkedremote computer for review by a clinician. S1 signals 402 are shown foreach of the VV interval settings 404. A setting of 0 ms results insimultaneous RV and LV pacing pulse delivery. A positive setting resultsin the LV being paced earlier than the RV, and a negative settingresults in the RV being paced earlier than the LV. Thus the VV intervalsetting corresponds to the timing of an LV pacing pulse relative to anRV pacing pulse.

The S1 amplitude 456 is observed to be maximized at a VV interval of −20ms. This maximum S1 amplitude 456 is also observed to correspond to amerging of the M1 and T1 signals corresponding to closure of the mitraland tricuspid valves, respectively compared to the S1 signal recordedfor other VV intervals. For example, at a VV interval of 20 ms, the M1signal 460 and the T1 signal 462 are observed to separate resulting inan overall lower S1 amplitude. A plot of the M1-T1 separation timeand/or S1 amplitude as a function of VV interval may be generatedsimilar to the plot shown in FIG. 5 for AV delay to allow a clinician oruser to observe the trend of the HS parameters with respect to VVinterval and facilitate selection of an optimal VV interval setting.

FIG. 7 is a flow chart 500 of a method for selecting pace controlparameters using HS signal analysis. At block 502, the process isinitiated, automatically or in response to a user command. The processmay be initiated automatically on a periodic basis or triggered inresponse to another monitored signal, which may be a physiologicalsignal such as an EGM or ECG, HS, pressure, oxygen, activity or posturesignal. Other monitored signals or measurements which may triggerinitiation of the process shown in flow chart 500 may include leadimpedance measurements, capture threshold measurements, or detection ofloss of capture.

The process shown in flow chart 500 is performed to identify an optimalpacing vector when multiple pacing vectors are available for pacing in aparticular heart chamber. For example, in FIG. 2, a multi-polar lead isshown to include four electrodes 144 positioned for pacing in the LV132. The four electrodes can be referred to as LV1 through LV4. At leastsixteen bipolar pacing vectors are available using all bipolarcombinations of electrodes 144 as well as at least four unipolar pacingvectors using each of electrodes 144 selected one at a time with ananode located away from the LV, such as an IMD housing electrode or RVcoil electrode 162 or RV tip electrode 140. Different pacing sitescorresponding to the location of each of electrodes LV1 through LV4 144and different electrode vectors may produce different hemodynamicresponse to the pacing therapy.

At block 504, a first pacing vector is selected for testing frommultiple pacing vectors available for pacing in a given heart chamber.At block 506, a pacing timing parameter, such as an AV interval or VVinterval, is varied during pacing delivered using the selected pacingvector. HS signals are acquired for each pacing timing parameter settingat block 508, by advancing to a next timing parameter setting at block512 until all timing parameter settings have been applied as determinedat decision block 510.

In one embodiment, starting the iterative adjustment of the timingparameter at block 506 includes determining an initial setting based onhistorical data. For example, the IMD 10 may determine an intrinsic AVconduction time based on a sensed atrial P-wave and a sensed ventricularR-wave or an atrial pacing pulse and a sensed ventricular R-wave. Thepacing history may also be used to determine a lower pacing rate duringthe iterative process. For example, a lower rate resulting in at least90% atrial paced beats and an AV interval approximately equal to or justgreater than the measured intrinsic AV conduction time may be set as theinitial pace timing parameters at block 506. The AV interval is theniteratively reduced, e.g. by 20 ms decrements until a minimum AVinterval test setting is reached. Each AV interval may be applied for adata acquisition time interval, for example 20 seconds or more, duringwhich HS signals are acquired.

If all timing parameter settings have been tested, as determined atblock 510, the next pacing vector is selected at block 516 until alltest pacing vectors have been applied as determined at decision block514. After obtaining HS signals for multiple settings of a pacing timingparameter for all test pacing vectors, a HS parameter trend with respectto the timing parameter is determined for each pacing vector. The HSparameter trends are compared between pacing vectors at block 518.

The HS trend with respect to timing parameter may present differentbehaviors between pacing vectors. For example the trend may be generallyflat for one vector and generally bell-shaped for another vector. Inanother example, the trend may be monotonically increasing or decreasingfor one vector and having a sudden slope change for another vector. Aparticular trend may be indicative of a more favorable response to thepacing therapy. For example, if the HS parameter being evaluated is theV-S2 interval with respect to AV interval, a desired trend may include asudden change in the trend, for example a sudden change from a generallyflat trend to a decreasing trend. If the HS parameter being evaluated isS1 amplitude, a desired trend may be a generally bell-shaped curvehaving a recognizable peak.

If a desired trend indicating a positive hemodynamic response to thepacing therapy is not found for at least one pacing vector, asdetermined at decision block 519, the pacing lead may be repositioned atblock 521 when the process shown by flow chart 500 is being performedduring an initial implant procedure.

Alternatively, if the desired trend is not found, a default pacingvector or a vector having the next most favorable HS parameter trend maybe selected. If the desired trend is observed for at least one vector, avector having the desired trend is selected at block 520. For example, apacing vector presenting a sudden change in the V-S2 interval trend withrespect to AV interval may be selected. In another example, a pacingvector presenting a generally bell-shaped curve of the S1 amplitude maybe selected. If more than one vector presents the desired trend, thevector presenting the greatest response of the HS parameter to thevarying pace timing parameter may be selected, e.g. the greatest maximumpeak of the HS parameter, greatest range of values, longest AV intervalassociated with a peak or inflection point, etc. Alternatively, if morethan one vector presents the desired trend, additional HS parameters maybe evaluated to select the optimal pacing vector at block 520.

At block 522, the trend of at least one HS parameter is evaluated as afunction of the timing parameter for the selected pace vector. Anoptimal timing parameter setting is identified at block 524, for exampleusing the methods described above. In one embodiment, a pace vector maybe selected based on a trend of on HS parameter and then the trend of adifferent HS parameter may be used to determine an optimal timingcontrol parameter. At block 526, a report of the HS data may begenerated and displayed including trends of the measured HS parameterswith respect to a pace control parameter. The selected pace vector andoptimal timing parameter may be automatically programmed at block 528,or programmed by a user upon accepting the recommended values.

Thus, a medical device system and associated methods have been presentedin the foregoing description with reference to specific embodiments. Itis appreciated that various modifications to the referenced embodimentsmay be made without departing from the scope of the disclosure as setforth in the following claims.

The invention claimed is:
 1. A medical device system, comprising: aplurality of electrodes for delivering cardiac pacing pulses to apatient's heart; a cardiac sensing module coupled to the plurality ofelectrodes; a cardiac pacing module coupled to the plurality ofelectrodes for generating cardiac pacing pulses and controlling deliveryof the pacing pulses at a plurality of pace parameter settings; anacoustical sensor for obtaining heart sound signals; a processor enabledto: control the pacing module to deliver the cardiac pacing pulses atthe plurality of pace parameter settings comprising a plurality ofsettings of a pacing time interval, receive the heart sound signalsduring the delivery of the cardiac pacing pulses at the plurality ofpace parameter settings comprising the plurality of settings of thepacing time interval, derive a plurality of heart sound signalparameters from the heart sound signals, the heart sound signalparameters comprising at least a first heart sound signal parameter anda second heart sound signal parameter, wherein the first heart soundsignal parameter comprises a V-S2 interval measured as a time intervalbetween a ventricular electrical event and an S2 heart sound for each ofthe plurality of settings of the pacing time interval, determine a trendof at least the V-S2 interval with respect to the plurality of settingsof the pacing time interval, identify an inflection point of the trendof the V-S2 interval, identify one of the plurality of settings of thepacing time interval that occurs at the identified inflection point as amaximum optimal setting of the pacing time interval, determine a trendof the second heart sound signal parameter with respect to the pluralityof settings of the pacing time interval, the second heart sound signalparameter different than the V-S2 interval, and identify an optimalsetting of the pacing time interval from the plurality of settings ofthe pacing time interval that corresponds to a maximum value of thesecond heart sound signal parameter when the pacing time interval isequal to or less than the identified maximum optimal setting of thepacing time interval; and an external display configured to present thetrend of at least one of the V-S2 interval or the second heart soundsignal parameter with respect to the plurality of settings of the pacingtime interval.
 2. The system of claim 1, wherein the external display isfurther configured to present the identified optimal setting of thepacing time interval from the plurality of settings of the pacing timeinterval that corresponds to the maximum value of the second heart soundsignal parameter when the pacing time interval is equal to or less thanthe identified maximum optimal setting of the pacing time interval. 3.The system of claim 1, wherein the plurality of electrodes comprises aplurality of electrodes positioned along a ventricular chamber, theplurality of pace parameter settings comprising a plurality of pacingvectors selected from the plurality of electrodes positioned along aventricular chamber.
 4. The system of claim 3, wherein the cardiacpacing module is configured to deliver pacing pulses using each of theplurality of pacing vectors and, for each of the plurality of pacingvectors, deliver pacing pulses at each of the plurality of settings ofthe pacing time interval.
 5. The system of claim 4, wherein theprocessor is configured to determine a trend of at least one of theplurality of heart sound signal parameters with respect to the pluralityof settings of the pacing time interval for each of the plurality ofpacing vectors, and identify an optimal pacing vector in response to thetrends with respect to the plurality of pacing time interval settings.6. The system of claim 5, wherein the processor is configured todetermine the trend of the V-S2 interval with respect to the pluralityof settings of the pacing time interval for the optimal pacing vector.7. The system of claim 4, wherein the plurality of electrodes comprisesa plurality of electrodes positioned along a left ventricle of thepatient's heart and the plurality of pacing time interval settingscomprises a plurality of atrial-ventricular intervals.
 8. The system ofclaim 7, wherein the processor is configured to identify the optimalpacing vector in response to one of the plurality of pacing vectorspresenting a desired trend.
 9. The system of claim 8, wherein thedesired trend comprises a generally bell-shaped trend having a maximumpeak.
 10. The system of claim 8 wherein the desired trend comprises asudden slope change.
 11. A medical device system, comprising: aplurality of electrodes for delivering cardiac pacing pulses to apatient's heart; a cardiac sensing module coupled to the plurality ofelectrodes; a cardiac pacing module coupled to the plurality ofelectrodes for generating cardiac pacing pulses and controlling deliveryof the pacing pulses at a plurality of pace parameter settings; anacoustical sensor for obtaining heart sound signals; a processor enabledto: control the pacing module to deliver the cardiac pacing pulses atthe plurality of pace parameter settings comprising a plurality ofsettings of an atrial-ventricular interval, receive the heart soundsignals during the delivery of the cardiac pacing pulses at theplurality of pace parameter settings comprising the plurality ofsettings of the atrial-ventricular interval, derive a plurality of heartsound signal parameters from the heart sound signals, the heart soundsignal parameters comprising at least a V-S2 interval measured as a timeinterval between a ventricular electrical event and an S2 heart soundfor each of the plurality of settings of the atrial-ventricularinterval, determine a trend of the V-S2 interval with respect to aplurality of settings for the atrial-ventricular interval, identify asudden change from a flat slope to a descending slope of the trend ofthe V-S2 interval, and identify one of the plurality of settings for theatrial-ventricular interval at which the sudden change from the flatslope to the descending slope of the determined V-S2 trend occurs as amaximum optimal setting of the atrial-ventricular interval; and anexternal display configured to present the trend of the V-S2 intervalwith respect to the plurality of settings for the atrial-ventricularinterval.
 12. The system of claim 11, wherein the external display isfurther configured to present the maximum optimal setting of theatrial-ventricular interval.
 13. The system of claim 11, wherein theplurality of electrodes comprises a plurality of electrodes positionedalong a ventricular chamber, the plurality of pace parameter settingscomprising a plurality of pacing vectors selected from the plurality ofelectrodes positioned along a ventricular chamber.
 14. The system ofclaim 13, wherein the cardiac pacing module is configured to deliverpacing pulses using each of the plurality of pacing vectors and, foreach of the plurality of pacing vectors, deliver pacing pulses at eachof the plurality of settings of the atrial-ventricular interval.
 15. Thesystem of claim 14, wherein the processor is configured to determine atrend of the V-S2 interval with respect to the plurality of settings ofthe atrial-ventricular interval for each of the plurality of pacingvectors, and identify an optimal pacing vector in response to the trendswith respect to the plurality of atrial-ventricular interval settings.16. The system of claim 15, wherein the processor is further configuredto determine a second trend of the V-S2 interval with respect to theplurality of settings of the atrial-ventricular interval for the optimalpacing vector and identify an optimal setting of the atrial-ventricularinterval in response to the second trend.
 17. The system of claim 15,wherein the processor is configured to identify the optimal pacingvector in response to a pacing vector presenting a desired trend. 18.The system of claim 17, wherein the desired trend comprises a generallybell-shaped trend having a maximum peak.
 19. The system of claim 17,wherein the desired trend comprises a sudden slope change.
 20. Thesystem of claim 14, wherein the plurality of electrodes comprises aplurality of electrodes positioned along a left ventricle of thepatient's heart.
 21. A medical device system, comprising: a plurality ofelectrodes for delivering cardiac pacing pulses to a patient's heart; acardiac sensing module coupled to the plurality of electrodes; a cardiacpacing module coupled to the plurality of electrodes for generatingcardiac pacing pulses and controlling delivery of the pacing pulses at aplurality of pace parameter settings, wherein the plurality of paceparameter settings comprises a plurality of pacing vectors selectablefrom the plurality of electrodes; an acoustical sensor for obtainingheart sound signals; a processor enabled to: control the pacing moduleto deliver the cardiac pacing pulses at the plurality of pace parametersettings comprising a plurality of settings of a pacing time interval,receive the heart sound signals during the delivery of the cardiacpacing pulses at the plurality of pace parameter settings comprising theplurality of settings of the pacing time interval, derive a plurality ofheart sound signal parameters from the heart sound signals, the heartsound signal parameters comprising at least a V-S2 interval measured asa time interval between a ventricular electrical event and an S2 heartsound for each of the plurality of settings of the pacing time interval,determine a trend of at least the V-S2 interval with respect to theplurality of settings of the pacing time interval, identify aninflection point of the trend of the V-S2 interval, identify one of theplurality of settings of the pacing time interval that occurs at theidentified inflection point as a maximum optimal setting of the pacingtime interval, for each of the plurality of pacing vectors determine atrend of at least one of the plurality of heart sound signal parameterswith respect to the plurality of settings of the pacing time interval,compare a shape of each of the determined trends over the plurality ofsettings of the pacing time interval to a desired shape of the trend,determine whether at least one of the plurality of pacing vectors has atrend matching the desired shape, and identify an optimal pacing vectorfrom the plurality of pacing vectors when at least one of the pluralityof pacing vectors has a trend matching the desired shape; and anexternal display configured to present the trend of at least one of theplurality of heart sound signal parameters with respect to the pluralityof settings of the pacing time interval.
 22. The system of claim 21,wherein the processor is further configured to: determine the trend foreach of the plurality of pacing vectors as the trend of the V-S2interval with respect to the plurality of settings of the pacing timeinterval; compare the shapes of each of the determined V-S2 intervaltrends to a desired shape of the V-S2 interval trend comprising a suddenchange from a flat slope to a decreasing slope; when at least one of theV-S2 interval trends determined for the plurality of pacing vectorsmatches the desired shape, identify the optimal pacing vector as thepacing vector having the V-S2 interval trend matching the desired shape;identify the maximum optimal setting as one of the plurality of settingsof the pacing time interval that occurs at the sudden change; and selectan optimal setting of the pacing time interval that is less than orequal to the maximum optimal setting for delivering therapeutic pacingpulses using the optimal pacing vector.
 23. The system of claim 21,wherein the external display is further configured to present themaximum optimal setting of the pacing time interval.